PSMA PET/CT-Guided SBRT Plus Darolutamide in mHSPC

Inclusion Criteria:

* Male participants aged ≥18 years and \<85 years.
* Histologically confirmed prostate adenocarcinoma.
* No neuroendocrine carcinoma, ductal adenocarcinoma, small-cell carcinoma, signet-ring cell carcinoma, or sarcomatoid carcinoma component.
* Metastatic prostate cancer confirmed by imaging and/or pathological evidence.
* Baseline PSMA PET/CT assessment demonstrates a total of ≤20 metastatic lesions.
* No prior radical prostatectomy or radiotherapy for prostate cancer.
* No prior systemic anti-tumor therapy that may affect the efficacy assessment of this study, including androgen receptor signaling inhibitors (ARSIs; e.g., abiraterone, enzalutamide, apalutamide, rezvilutamide, or darolutamide), chemotherapy, PARP inhibitors, radionuclide therapy, or other such treatments.
* Short-term androgen deprivation therapy (ADT) and/or first-generation antiandrogen therapy prior to enrollment is permitted, provided that the interval from the first initiation of any such treatment to the date of enrollment does not exceed 3 months (≤12 weeks).
* Expected survival \>12 months.
* Able to understand the study and voluntarily sign written informed consent.
* Able and willing to comply with study visits and protocol procedures.
* Willing to provide tumor tissue, blood, and other biological samples as required by the study protocol.
* Absolute neutrophil count ≥1.5 × 10\^9/L.
* Platelet count ≥100 × 10\^9/L.
* Hemoglobin ≥90 g/L.
* Total bilirubin ≤1.5 × upper limit of normal.
* Alanine aminotransferase and aspartate aminotransferase ≤2.5 × upper limit of normal.
* Serum albumin ≥20 g/L.
* Serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥50 mL/min.
* Eastern Cooperative Oncology Group performance status ≤2.

Exclusion Criteria:

* Current or prior history of another primary malignancy.
* History of another malignancy within 3 years that differs from the study cancer in primary site or histology.
* History of papillary thyroid carcinoma is allowed if it is well controlled.
* History of basal cell carcinoma of the skin is allowed if it is well controlled.
* History of squamous cell carcinoma of the skin is allowed if it is well controlled.
* History of cervical carcinoma in situ is allowed if it is well controlled.
* Prior radical prostatectomy.
* Prior external beam radiotherapy.
* Prior radical or ablative local therapy for prostate cancer.
* Prior treatment with an androgen receptor signaling inhibitor, including abiraterone, enzalutamide, apalutamide, rezvilutamide, or darolutamide.
* Prior chemotherapy for prostate cancer.
* Major surgery within 4 weeks before enrollment.
* Serious trauma within 4 weeks before enrollment.
* Contraindication to radiotherapy.
* Spinal cord compression.
* Active enteritis.
* Severe pelvic infection.
* Inability to maintain the required body position for radiotherapy.
* History of allergy to PET/CT tracer.
* Nuclear medicine assessment showing super bone imaging.
* Marked discordance between PSMA PET/CT and FDG PET/CT findings.
* Disease progression during the 6-month run-in period of androgen deprivation therapy plus darolutamide before randomization.
* Unacceptable toxicity during the 6-month run-in period of androgen deprivation therapy plus darolutamide before randomization.
* No active tumor lesion on PSMA PET/CT after the 6-month run-in period.
* Allergy to any component of the study treatment.
* Active or poorly controlled serious infection.
* Human immunodeficiency virus infection.
* Acute or chronic active hepatitis B infection, defined as positive hepatitis B surface antigen with hepatitis B virus DNA \>1 × 10\^3/mL.
* Acute or chronic active hepatitis C infection, defined as positive hepatitis C virus antibody with hepatitis C virus RNA \>15 IU/mL.
* Active pulmonary tuberculosis.
* Other serious infectious disease.
* New York Heart Association class III or IV congestive heart failure.
* Persistent symptomatic arrhythmia.
* Uncontrolled atrial fibrillation.
* Left ventricular ejection fraction below the lower limit of normal on repeated echocardiographic assessments.
* Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg.
* Arterial thrombotic, embolic, or ischemic event within 6 months before enrollment.
* Myocardial infarction within 6 months before enrollment.
* Unstable angina within 6 months before enrollment.
* Cerebrovascular accident within 6 months before enrollment.
* Transient ischemic attack within 6 months before enrollment.
* Medical condition requiring warfarin or coumarin anticoagulation therapy.
* Uncontrolled hypercalcemia, defined as ionized calcium \>1.5 mmol/L, total calcium \>12 mg/dL, or corrected serum calcium above the upper limit of normal.
* Symptomatic hypercalcemia requiring continuous bisphosphonate therapy.
* Uncontrolled adrenal insufficiency.
* History of abdominal fistula within 6 months before enrollment.
* History of gastrointestinal perforation within 6 months before enrollment.
* History of intra-abdominal abscess within 6 months before enrollment.
* Severe non-healing wound.
* Severe non-healing ulcer.
* Gastrointestinal disease that may impair absorption.
* Active peptic ulcer disease.
* Uncontrolled nausea.
* Uncontrolled vomiting.
* Uncontrolled diarrhea.
* History of small bowel resection that may impair drug absorption.
* Other acute or chronic disease, psychiatric disorder, or laboratory abnormality that may increase the risk associated with study participation or study treatment.
* Other acute or chronic disease, psychiatric disorder, or laboratory abnormality that may interfere with interpretation of study results.
* Any other medical or psychological condition that, in the investigator's judgment, may affect participant safety, compliance, or study integrity.
* Any condition that, in the investigator's judgment, makes the participant unsuitable for this study.